Although successful pregnancies may be possible for many women with inflammatory bowel disease (IBD), outcomes depend on disease activity at the time of conception. Recent studies suggest that pregnant women with quiescent Crohn's disease or ulcerative colitis are at higher risk of venous thromboembolism and emergency cesarean delivery than are women without those conditions. But active disease, with its circulating proinflammatory cytokines, increases the risk of other complications, including still birth, premature delivery and low birth weight infants.
Maintaining control of IBD before and during pregnancy is crucial — with medications and, when flares occur, with hospitalization and more-aggressive measures — according to Sunanda V. Kane, M.D., of Mayo Clinic in Rochester, Minn.
"We've come a long way from the days when we thought patients couldn't take any medications because they were pregnant," she says. "Even for medications that have a category D rating, there are situations where the benefits outweigh the risks. Active disease is a worse scenario for pregnancy than active medicine. It is better to keep someone well than try to play catch-up in the short amount of time we have before the baby feels the effects of mom's ill health."
Still, some IBD medications remain controversial for pregnant patients. One of the safest, mesalamine, or 5-aminosalicylic acid (5-ASA), is known to cross the placenta, but studies have not found an increased incidence of fetal abnormalities in women taking it. "We have a great deal of controlled prospective data to show that most women are fine on this medication during pregnancy and nursing," Dr. Kane says.
Asacol, a brand of 5-ASA with a recently downgraded rating, is an exception. In animal studies, dibutyl phthalate, an inactive ingredient in the enteric coating of Asacol and Asacol HD tablets, was associated with urogenital abnormalities at doses greater than 80 times the human dose — the equivalent of about 200 pills a day.
"I have been prescribing Asacol for 20 years, and I don't see that signal in clinical practice," notes Dr. Kane. "But we now have the PIANO registry with a cohort of 1,100 enrolled women, and there is a small signal that Asacol, unlike other 5-ASAs, may increase the risk of congenital anomalies. I have colleagues who now will stop Asacol and switch to another 5-ASA compound for pregnant patients."
The immunomodulators mercaptopurine and azathioprine are category D medications — a designation from the 1950s when the drugs were first approved to treat leukemia. Doses used to treat IBD are smaller and are considered low risk, Dr. Kane says, although in one study, women treated with both azathioprine and a biologic had a fivefold increase in spontaneous abortion.
"It has been our practice to continue immunomodulator therapy through pregnancy. Stopping medication when a woman becomes pregnant only increases the risk of a flare," she points out. But she never starts pregnant women on mercaptopurine or azathioprine because of the time it takes the drug to become effective and because pancreatitis can be much more serious in pregnant patients.
Biologics — aggressive therapies with short track records — raise the most red flags. Infliximab (Remicade) and adalimumab (Humira) are IgG1 antibodies that can cross the placenta. A few small studies suggest these drugs can be used safely in pregnant women with active Crohn's disease, but the number of patients involved is too low to draw firm conclusions.
Certolizumab (Cimzia), a Fab prime fragment of a tumor necrosis factor inhibitor, does not cross the placenta — a potentially significant advantage, according to Dr. Kane. "If a woman is childbearing age and needs a biologic, then we will give her certolizumab," she says. "But we will never switch biologics during pregnancy; it's dangerous and not necessarily successful. This is not cookbook medicine — it's very individualized. Ultimately, it comes down to sharing the data and discussing with each patient the risk-to-benefit ratio of biologic therapy during pregnancy. Then, the patient, gastroenterologist and obstetrician together can make an informed decision."
She adds that the vast majority of women do well if they have the right education and counseling before becoming pregnant. "Women with IBD have a higher voluntary childless rate because they've been told they shouldn't get pregnant. Certainly, it's not a good time to get pregnant if a patient has active, complicated disease. But I don't say, 'No, you should never get pregnant.' I say, 'Give me six to eight months to get you better.' "